Magnetic resonance spectroscopy reveals an epileptic network in juvenile myoclonic epilepsy

Purpose: To investigate the cerebral metabolic differences between patients with juvenile myoclonic epilepsy (JME) and normal controls and to evaluate to what extent these metabolic alterations reflect involvement of an epileptic network. Methods: Sixty patients with JME were submitted to multi‐voxel proton spectroscopy (1H‐MRS) at 1.5 T over medial prefrontal cortex (MPC), primary motor cortex (PMC), thalamus, striatum, posterior cingulate gyrus (PCG), and insular, parietal, and occipital cortices. We determined ratios for integral values of N‐acetyl‐aspartate (NAA) and glutamate‐glutamine (GLX) over creatine‐phosphocreatine (Cr). The control group (CTL) consisted of 30 age‐ and sex‐matched healthy volunteers. Results: The NAA/Cr ratio, a measure of neuronal injury, was reduced in PMC, MPC, and thalamus among patients. In addition, they had an altered GLX/Cr ratio, which is involved in excitatory activity, on PMC, MPC, and PCG, where it was reduced, whereas it was increased on insula and striatum. Multiple regression analysis revealed the strongest correlation between thalamus and MPC, but the thalamus was also correlated with insula, occipital cortex, and striatum among patients. Lower NAA/Cr was observed with advancing age and duration of epilepsy, regardless of frequency of seizures and antiepileptic drug therapy in thalamus and frontal cortex. Discussion: The identification of a specific network of neurochemical dysfunction in patients with JME, with diverse involvement of particular structures within the thalamocortical circuitry, suggests that cortical hyperexcitability in JME is not necessarily diffuse, supporting the knowledge that the focal/generalized distinction of epileptogenesis should be reconsidered. Furthermore, evidence is provided toward progressive neuronal dysfunction in JME.     

Proton magnetic resonance spectroscopy study of bilateral thalamus in juvenile myoclonic epilepsy.

PURPOSE: To investigate neuronal dysfunction in the thalami of juvenile myoclonic epilepsy (JME) by using proton magnetic resonance spectroscopy (MRS). METHODS: We performed single-voxel proton MRS over the right and the left thalami of 15 consecutive patients (10 women, 5 men) with JME (mean age 20.3 years) and 16 healthy volunteers (10 women, 6 men) (mean age 24.5 years). All patients had seizure onset in late childhood-teenage, normal neurologic examination, typical electroencephalogram (EEG) of JME and normal magnetic resonance imaging (MRI). We determined N-acetylaspartate (NAA) values and NAA over creatine-phosphocreatine (Cr) values. Mann-Whitney U-test was used to evaluate group differences. RESULTS: Group analysis showed that echo time (TE) 270 integral value of NAA over left thalamus were significantly decreased in JME patients as compared with controls (34.6033+/-15.8386; 48.0362+/-22.2407, respectively, P=0.019). Also group analysis showed that thalami NAA/Cr ratios were significantly decreased in JME patients (right side, 2.21+/-1.07; left side 2.00+/-0.72) as compared with controls (right side, 3.45+/-1.50; left side, 3.08+/-1.60; P=0.011 and P=0.030, respectively). CONCLUSION: In the previous studies, NAA values in patients with JME found that they were not statistically lower in thalami than control group. But, in our study, NAA value was found low as well. It has been known that NAA is a neuronal marker and hence it is a valuable metabolite in the neuron physiopathology. As a result, in the patients with JME we tried to support the theory that the underlying mechanism of the generalized seizures was the abnormal thalamocortical circuity, determining the thalamic neuronal dysfunction in MRS statistically.     

Cortical excitability in juvenile myoclonic epileptic patients and their asymptomatic siblings: A transcranial magnetic stimulation study

In this study, we aimed to evaluate motor cortical excitability changes in patients with juvenile myoclonic epilepsy (JME) and their asymptomatic siblings (AS) using single-pulse transcranial magnetic stimulation (spTMS). 21 patients with JME and their 21 AS were compared to 20 healthy controls. All of JME patients were receiving antiepileptic therapy and their seizures were well controlled. Firstly, standard EEG examinations and then TMS studies were performed. Resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, the durations of central motor conduction time (CMCT) and cortical silent period (CSP) were measured. After TMS studies, EEG recordings were repeated in an hour to evaluate any effect of TMS study on EEG. There were no significant differences between the first and second EEG recordings. No seizures were recorded during and after the TMS study. RMT was found higher in JME patients than AS and normal controls. There were no significant differences between cortical MEP amplitudes and MEP amplitude/CMAP (compound muscle action potential) amplitude ratio in all three groups. CMCT duration was shorter in JME patients than AS. CSP durations of JME patients were found to be longer than controls. In AS, CSP durations were also found to be longer than controls but this difference was not found statistically significant. Our results suggested that although high MT may be related to antiepileptic therapy, the prolongation of CSP duration may reflect impairment of supraspinal and/or intracortical inhibitory mechanism in JME. To eliminate the drug effect, further studies are needed in newly diagnosed JME patients without medication and large series of their asymptomatic siblings.     

The relationship between white matter abnormalities and cognitive functions in new-onset juvenile myoclonic epilepsy

Diffusion tensor imaging (DTI) has revealed evidence of subcortical white matter abnormalities in the frontal area in juvenile myoclonic epilepsy (JME). Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in the corticothalamic pathway have been detected in adult patients with JME. It has been demonstrated that, in adult patients with JME, frontal dysfunction is related to subcortical white matter damage and decreased volume in frontal cortical gray matter and the thalamus. Many studies have focused on adult patients.Twenty-four patients and 28 controls were evaluated. The group with JME had significantly worse results for the word fluency, trail-B, and Stroop tests that assessed executive functions. A significant decrease in FA values in the dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the right thalamus, the posterior cingulate, the corpus callosum anterior, the corona radiata, and the middle frontal white matter (MFWM) and an increase in ADC values in patients with JME were detected. The correlation between FA values in DLPFC and the letter fluency test results was positive, and the correlation with the Stroop and trail-B test results was negative. We found a negative correlation between SMA, anterior thalamus, and MFWM FA values and the trail-B test results and a positive correlation between the SMA, anterior thalamus, and MFWM FA values and the letter fluency test results.We detected white matter and gray matter abnormalities in patients with new-onset JME using DTI. In addition, we determined the relationship between cognitive deficit and microstructural abnormalities by evaluating the correlation between the neuropsychological test battery results and DTI parameters. We evaluated newly diagnosed patients with JME in our study. That leads us to believe that microstructural abnormalities exist from the very beginning of the disease and that they result from the genetic basis of the disease.     

轻度认知损害患者氢质子磁共振波谱随访研究

目的回顾分析并总结轻度认知损害(MCI)患者认知功能转归及脑组织代谢物氢质子磁共振波谱(~1H-MRS)特点。方法采用简易智能状态检查量表(MMSE)和蒙特利尔认知评价量表(Mo CA)评价75例轻度认知损害患者和17例性别、年龄、受教育程度相匹配的正常对照者的认知功能,1H-MRS检测左侧海马和左侧额叶代谢物[包括N-乙酰天冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)、肌醇(m I)、谷氨酸复合物(Glx)]表达变化。结果与正常对照者相比,轻度认知损害患者左侧海马和左侧额叶Glx/Cr比值均降低(P=0.030,0.030)。至随访结束时,MCI组7例(9.33%)进展为阿尔茨海默病、55例(73.33%)认知功能无变化、13例(17.33%)逆转为认知功能正常;正常对照组13例(13/17)认知功能功能无变化,2例(2/17)进展为轻度认知损害,无一例进展为阿尔茨海默病。不同认知功能转化亚组中仅MCI-MCI组患者Glx/Cr比值高于MCI-AD组(P=0.040)。结论左侧海马和左侧额叶Glx/Cr比值降低可能是轻度认知损害患者认知功能恶化较敏感的生物学指标,尚待扩大样本量、延长随访时间深入研究。     

Event-related potentials and cognitive functions in epileptic treated patients

Antiepileptic drugs as well epilepsy itself are known to induce some cognitive impairment. Thirty-six epileptic patients under unchanged and reduced therapy conditions were followed from a clinical (seizures' evaluation, reaction times [RTs], memory tests) and neurophysiological (EEG, BAEPs, ERPs) point of view, weekly as inpatients (mean stay 8.9 weeks) and after 1 and 3 months as outpatients. This study showed on one hand no clear correlation between RTs and ERPs components, and on the other hand an improvement of the most complex RT after reduction of polytherapy or stabilization of seizures by the introduction of carbamazepine-CR in newly treated patients. These data suggest that in epileptic patients there exists a slowing of cognitive processes between the stimulus evaluation time and the motor response and that this step is improved when a reduced but efficient therapy is given.     

氢质子MR波谱对弥漫性轴索损伤的评估

景：目前在弥漫性轴索损伤的临床诊断和伤情评估上,CT和常规MRI的作用非常有限。 目的：验证氢质子MR波谱技术在弥漫性轴索损伤临床诊断及预后评估中的价值。 设计、时间及地点：前瞻性临床对照观察,于2002-10/2007-09在重庆医科大学附属第一医院神经外科及放射科完成。 对象：纳入63例颅脑损伤患者,根据MRI检查结果分为2组,弥漫性轴索损伤组27例,非弥漫性轴索损伤组36例;再利用单纯随机抽样法选择20名健康成年人作为正常对照。 方法：患者入院后,按常规进行治疗,一旦生命体征和意识情况允许,立即行包括液体衰减反转恢复序列在内的磁共振影像学检查,并在此同时行氢质子MR波谱检查,氢质子MR波谱检查数据进行后期工作站分析,并结合临床情况进行分析。 主要观察指标：胼胝体膝部、压部和基底核N-乙酰天冬氨酸/肌酸和磷酸肌酸、胆碱复合物/肌酸和磷酸肌酸、肌醇/肌酸和磷酸肌酸以及谷氨酸和谷氨酰胺/肌酸和磷酸肌酸等指标。 结果：与对照组和非弥漫性轴索损伤组相比,弥漫性轴索损伤组胼胝体膝部、压部和基底核出现N-乙酰天冬氨酸/肌酸和磷酸肌酸降低及胆碱复合物/肌酸和磷酸肌酸升高(P < 0.05~0.01),胼胝体膝部和压部出现肌醇/肌酸和磷酸肌酸及谷氨酰胺/肌酸和磷酸肌酸升高(P < 0.05)。与对照组相比,非弥漫性轴索损伤组出现胼胝体膝部胆碱复合物/肌酸和磷酸肌酸升高和压部N-乙酰天冬氨酸/肌酸和磷酸肌酸降低(P < 0.01),但变化程度比弥漫性轴索损伤组低。弥漫性轴索损伤组胼胝体膝部的胆碱复合物/肌酸和磷酸肌酸和伤后原发昏迷时间呈正相关(r=0.824,P < 0.01)。 结论：胼胝体膝部、压部和基底核各氢质子MR波谱指标可作为弥漫性轴索损伤有效的诊断指标。氢质子MR波谱中的胆碱复合物/肌酸和磷酸肌酸等指标可以很好地反映伤后组织学的改变,是临床伤情预测的灵敏指标。     

Exacerbation of tonicoclonic seizures in a juvenile myoclonic epileptic taking lamotrigine

INTRODUCTION: Lamotrigine is an anti-epileptic drug considered as a first-line therapy in idiopathic generalised epilepsy. Lamotrigine is well-tolerated and secondary aggravation of epileptic syndromes has rarely been reported. CASE REPORT: We report the case of a 19 year-old man with juvenile myoclonic epilepsy in whom lamotrigine lead to the exacerbation of generalised tonico-clonic seizures, reversible when lamotrigine was stopped and substituted by valproic acid. CONCLUSION: Lamotrogine may induce exacerbation of generalised tonico-clonic seizures and myoclonic jerks in juvenile myoclonic epilepsy.     

慢性失眠障碍患者认知功能与核磁共振波谱成像的研究

目的 探讨慢性失眠障碍(Chronic insomnia disorder,CID)患者的认知功能和海马氢质子磁共振波谱成像(Proton magnetic resonance spectroscopy,¹H-MRS)特点。方法 收集自2017年1月1日-2020年1月1日就诊于新疆医科大学第五附属医院睡眠障碍门诊的60例CID患者,对照组选取同期门诊体检的60例无睡眠障碍的健康人群; 采用匹兹堡睡眠质量指数量表(Pittsburgh sleep quality index,PSQI)评估2组研究对象的睡眠质量; 分别采用简易智力状态检查量表(MMSE)和蒙特利尔认知评估量表(MoCA)评估2组研究对象的总体认知功能; 应用¹H-MRS技术检测2组双侧海马N-乙酰天门冬氨酸(NAA)、胆碱复合物(Cho)和肌酸(Cr)3种代谢物水平,并计算NAA/Cr和Cho/Cr比值。结果 CID组患者PSQI评分显著高于对照组(P<0.01); CID组MMSE评分与对照组比较无显著差异(P>0.05); CID组MoCA评分显著低于对照组(P<0.01),其中注意力、瞬时记忆、延时记忆以及视空间执行功能评分均显著低于对照组(P<0.01、0.01、0.01、0.05); CID组右侧海马NAA/Cr比值低于对照组(1.76±0.32 vs.2.06±0.48)(t=2.278,P=0.027); CID组双侧海马NAA/Cr比值无明显差异(t=1.425,P=0.168); C1D组患者PSQI总分及病程与MoCA评分呈负相关(r=-0.428,-0.355,P=0.006),与右侧海马NAA/Cr比值呈负相关(r=-0.352,-0.308,P=0.019)。结论 CID患者失眠严重程度及病程与MoCA评分、右侧海马NAA/Cr 比值有关,可能导致患者轻度认知功能障碍(MCI)及右侧海马可能存在神经元受损。     

Treatment of myoclonic seizures in patients with juvenile myoclonic epilepsy

Drug treatment of Juvenile myoclonic epilepsy (JME) is mainly based on clinical experience and prospective and retrospective studies, with little evidence from randomized clinical trials. There are no head-to-head comparisons between old and new antiepileptic drugs (AEDs) and no drugs licensed specifically for JME. Valproate is unquestionably the drug of the first choice in men with JME. In women, lamotrigine should be preferred regarding teratogenicity and side effects of valproate. In addition, levetiracetam and topiramate are effective and can be use in combination or as second line treatment. Some AEDs can aggravate JME. In addition of AEDs, non-pharmacological treatments are important in JME. JME usually require lifelong treatment because seizures nearly always return after withdrawal of therapy.     

Evaluation of neurodegeneration in a mouse model of infantile batten disease by magnetic resonance imaging and magnetic resonance spectroscopy

Neuronal ceroid lipofuscinoses (NCLs) represent a group of common hereditary childhood neurodegenerative storage disorders that have no effective treatment. Mutations in eight different genes cause various forms of NCLs. Infantile NCL (INCL), the most lethal disease, is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. The availability of Ppt1-knockout (Ppt1-KO) mice, which recapitulate virtually all clinical and pathological features of INCL, provides an opportunity to test the effectiveness of novel therapeutic strategies in vivo. However, such studies will require noninvasive methods that can be used to perform serial evaluations of the same animal receiving an experimental therapy. Thus, the development of noninvasive method(s) of evaluation is urgently needed. Here, we report our evaluation of the progression of neurodegeneration in Ppt1-KO mice starting at 3 months of age by MRI and MR spectroscopy (MRS) and repeating these tests using the same mice at 4, 5 and 6 months of age. Our results showed progressive cerebral atrophy, which was associated with histological loss of neuronal content and increase in astroglia. Remarkably, while the brain volumes in Ppt1-KO mice progressively declined with advancing age, the MRS signals, which were significantly lower than those of their wild-type littermates, remained virtually unchanged from 3 to 6 months of age. In addition, our results also showed an abnormality in cerebral blood flow in these mice, which showed progression with age. Our findings provide methods to serially examine the brains of mouse models of neurodegenerative diseases (e.g. Ppt1-KO mice) using noninvasive and nonlethal procedures such as MRI and MRS. These methods may be useful in studies to understand the progression of neuropathology in animal models of neurodegenerative diseases as they allow repeated evaluations of the same animal in which experimental therapies are tested.     

Prediction of cognitive decline after stroke using proton magnetic resonance spectroscopy

Structural MRI measures have been used to predict cognitive decline in elderly subjects, but few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) for this purpose, particularly after stroke. We studied the potential of (1)H-MRS to predict cognitive decline in patients with stroke or TIA and healthy ageing controls over 12 months and 3 years. Structural MRI and single-voxel (1)H-MRS in the frontal white matter and the occipito-parietal gray matter were performed at the index assessment (3-6 months post-stroke) in 49 stroke/TIA patients and 60 controls. Neuropsychological testing was performed at the index assessment and repeated at 12 months in 30 stroke/TIA patients and 49 controls, and at 3 years in 25 patients and 48 controls. In stroke/TIA patients, frontal NAA/Cr predicted cognitive decline over 12 months and 3 years, and in elderly control subjects frontal NAA predicted cognitive decline over 12 months only. In stroke/TIA patients, the (1)H-MRS measures were better predictors of cognitive decline than structural measures. (1)H-MRS may be useful in assessing early cognitive impairment after stroke/TIA and in normal ageing.     

脑梗死相关白质疏松患者磁共振波谱与认知功能关系的研究

目的研究脑梗死患者白质疏松的磁共振波谱表现特点,以及白质疏松的磁共振波谱与认知功能的关系,为血管性认知功能障碍的早期识别及防治提供依据。方法选择51例脑梗死伴白质疏松患者及21例非白质疏松者进行简易智能状态测验(MMSE)、画钟试验测试、Fuld物体记忆测验(FOM)、快速词汇测验(RVR)及WAIS数字广度测验;同时行头颅磁共振成像(MRI)及双侧额叶白质的磁共振波谱(MRS)检查,测定N-乙酰天门冬氨酸(NAA)、肌酸(Cr)及胆碱(Cho)的浓度。分析白质疏松的MRS表现特点及其与认知功能障碍的关系。结果重度脑白质疏松组Cho/Cr值明显高于无、轻及中度疏松组;Cho/Cr值与白质疏松程度呈正相关;左侧额叶白质NAA/Cr值与MMSE评分及画钟试验评分正相关;右侧Cho/Cr值与WAIS数字广度测验评分负相关。结论双侧额叶白质区MRS改变主要为Cho/Cr值升高,并且与白质疏松程度正相关。血管性认知障碍与双额叶白质区神经纤维损害不一定完全一致。     

The topographical distribution of epileptic spikes in juvenile myoclonic epilepsy with and without photosensitivity

Objective

Up to 30% of people with juvenile myoclonic epilepsy (JME) have photoparoxysmal responses (PPR). Recent studies report on structural and pathophysiological differences between people with JME with (JME+PPR) and without PPR (JME?PPR). We investigated whether electrophysiological features outside photic stimulation differ between these subtypes.

非痴呆型血管性认知障碍的磁共振波谱成像研究进展

血管性认知障碍（VCI）目前已成为老年人认知障碍的主要病因,其中,非痴呆型血管性认知障碍（VCIND）是VCI的初期阶段,具有可逆性。近年来,磁共振波谱（MRS）以其高分辨率、无创的特点,越来越广泛地应用于临床,成为了研究的热点。目前研究表明,VCIND患者的认知损害包括执行功能、视空间、感知功能、记忆力等几乎所有的主要认知域。MRS与认知量表的联合应用可提高VCIND的临床诊断的准确率。VCIND患者额叶、颞叶NAA/Cr降低较为明确,而丘脑仍需进一步研究。Cho在VCIND患者脑组织中的变化研究结果不甚一致。另外,MRS在M-aMCI与VCIND的鉴别中可起到重要的作用。关于VCIND的研究尚存在诸多问题,且结果差异较大,尚需进一步研究。